Link Between Gastrosplenic Damp-heat Syndrome, Bias In T Helper Type 1 (Th1)/Th2 CD4+T Cell Responses And HLA Class Ⅱ Polymorphisms

ObjectiveGastrosplenic damp-heat syndrome (GDS) is a common syndrome type of damp-heatsyndrome (DHS), as well as an important sthenia syndrome of Chinese medicine theory ofspleen and stomach. With the change in the way of life, particularly in the southern regionin China, GDS was particularly prevalent. GDS has extensive clinical basis, involvesvarious diseases, and most closely related to the diseases of the digestive system, especiallychronic gastritis for the first. Strong and vigorous spleen and stomach function is to ensurethat the organism to resist evils in virtue of spleen and stomach acquired for the foundationof life. Spleen and stomach closely related to the immune system. The current study showsthat the etiology of GDS is linked to Helicobacter pylori (H. pylori) infection. This paperstudies the local tissue inflammation and immune dysfunction in GDS may be related to H.pylori infection and immunoreaction subsequently. H. pylori infection may be activatedgastric local immune response and interferon (IFN)-gama and other cytokines, therebyinducing the surrounding epithelial cell expression of HLA classâ…¡molecules. That leads tolymphatic T helper (Th) cell subsets imbalance, there Thl cell response dominant. H. pyloristrains may also through gastric epithelial human leukocyte antigen (HLA) classâ…¡molecules-mediated host happen with closer interaction which led to a more significantgastric epithelial injury, as well as promote the immune response. To some extent, theimmune system can be considered to balance the Yin and Yang-conditioning systems,immune regulation also equivalent to the yin and yang balance adjustment. Th cells work akey role in the regulation of cellular and humoral immunity and specific immune andnon-specific immunity. Th1/Th2 balance, including its functions of cytokines interactionsbetween and mutual restraint, to some extent, reflects yin and yang to each other, mutualrestriction and generation and working together. Th1/Th2 balance of immune systemregulation reflected the pathology of GDS that varied by an association with yin evil andyang evil and the struggle healthy qi and pathogenic factor in organisms. And Th1/Th2balance also accorded with homeostasis between yin and yang opposing constraints,mutually restricting, eating and flowing in the process of GDS.The major histocompatibility complex (MHC) containing the human leukocyte antigen(HLA) is recognized as one of the most important genetic regions in relation to common human disease. The allelic and genetic structure of the MHC is complex. These extremelevels of polymorphism and dense genetic organization, including highly reiteratedsequences, correspond to so many differences of the individual constitution. And HLAallele frequencies also influenced by the geographical environment and so on. MeanwhileHLA classâ…¡gene polymorphism in a certain extent affected polarization, activity andproliferation of Th cell subsets. The current studies showed that spleen and stomach oftraditional Chinese medicine (TCM) are closely related to the immune system, and that thesyndrome types of TCM and body constitution were related to HLA genes. SpleenDeficiency Syndrome (SDS) may have some basis of immunogenetics. The constitutionalups and downs of spleen and stomach affect the susceptibility to disease and the conversionin the course of diseases.Therefore, we researched the relativity between the stomach-heat syndrome and H.pylori-related infection that diagnosed chronic superficial gastritis or peptic ulcer. And wemensurated the serum levels of interleukin (IL)-2, IL-4, IL-10 and IFN-gama, andcalculated IFN-gama/IL-4, so we may find out Th1/Th2 balance of immune cells in GDSfrom the results. At the same time we also studied the relativity between GDS and HLAclassâ…¡gene polymorphism, to search the gene type susceptible to GDS. Accordingly, wemay further reveal the biological basis and the mechanism of GDS, and know the formationof substance of GDS which to guide the diagnosis and treatment of GDS.MethodsWe selected 57 patients as case group, which diagnosed chronic superficial gastritisand peptic ulcer by gastroscopy from the medical wards in First Affiliated Hospital ofGuangzhou University of Chinese Medicine, and 15 normal cases as control group. Casegroup and control group were Guangdong native people of the Han nationality. Accordingto syndrome differentiation, case group was devided into two groups, which were GDSgroup (33cases) and SDS group (24 cases). The patients in GDS group and SDS group werechecked H. pylori infection by ¹⁴C-urea breath test. The serum levels of IL-2, IL-4, IL-10and IFN-gama in the three groups were mensurated by double-antibody sandwichenzyme-linked immunosorbent assay (ELISA), and were compared statistically. The allelesof HLA-DRB1 and HLA-DQA1 in three blood groups were detected by polymerase chainreaction-sequence specific primers (PCR-SSP) genotyping method.ResultThe infective rates of H. pylori in SDS group was remarkably higher than the rate inSDS group (P＜0.05)and the odds ratio (OR) is 3.733. That showed H. pylori infection wasrelated to GDS. The levels of IL-2 in GDS group and SDS group were higher than the levelin control group (P＜0.05), but the level of IL-2 was no significant difference in GDS groupand SDS group(P＞0.05). The level of IFN-gama and IFN-gama/IL-4 were higher in GDS group than in SDS group and control group (P＜0.05). Contrarily, the level of IL-4 waslower in GDS group than in SDS group and control group (P＜0.05). The level of IL-10 wasonly lower in GDS than in SDS (P＜0.05), but showed no significant difference with thelevel in control group (P＞0.05). In addition, the levels of IFN-gama and IFN-gama/IL-4were higher in H. pylori(+) group than in H. pylori(-) group (P＜0.05), but IL-2, IL-4 andIL-10 levels were not significantly different (P＞0.05).The gene frequency of DQA1^*0103 in SDS group was remarkably higher than innormal contrast group (P＜0.05), and OR was 4.48, but no statistical significant differencewas found between SDS group and SDS group(P＞0.05). On the contrary, the genefrequency of DQA1^*0601 in SDS group was remarkably lower than the other tow groups(P＜0.05), OR was 0.156. The data suggest that DQA1^*0103 and DQA1^*0601 is closelyassociated with SDS. But no statistical significant differences in carrier frequencies ofHLA-DRB1 alleles were evident (P＞0.05).ConclusionThe results showed that GDS in chronic superficial gastritis and peptic ulcer wasrelated to H. pylori infection. It was Th1/Th2 cellar immune imbalance that emerged in theorganism of GDS. There was Th1 cell response bias and cytokines network disorders as theresult of the increase of IL-2 level and IFN-gama level, the reduction of IL-4 level, andabnormity of IL-10 level. The bias of Th1/Th2 balance, embodied imbalance of immuneregulation, reflected the vivo imbalance between yin and yang, the struggle healthy qi andpathogenic factor. It may be one of lingering and refractory pathological mechanism ofdamp-heat syndrome that the Th1-type cytokines and Th2-type cytokines interactions andmutual constraints lead to the slow onset and potential lingering GDS. Moreover, theimbalance of Th1/Th2 immune deviation leaded by H. pylori infection may also cause Th1cell response domination in the organism of GDS. The data showed that HLA-DQA1^*0103was positively correlated genotype with GDS, and HLA-DQA1^*0601 was negativelycorrelated genotype. It suggested that GDS has a certain immunogenetic basis. HLA-DQA1^*0103 may be the susceptible gene to SDS, and DQA1^*0601 may be the protectivegene. HLA classâ…¡molecules encoded by HLA-susceptibility gene can identify andcertificate GDS infectious factor or antigenic irritant leading to GDS, submit to Th cells,and regulate Th cell proliferation and polarization, thus affects the immune response. It isthe cocontribution of HLA classâ…¡-susceptibility gene and Th1/Th2 cell immune balancethat result in GDS.Above all, because GDS may have immunogenetic susceptible factors and theinfectious pathogens, it will easily lead to weak functions of spleen and stomach and vivoaccumulation of dampness. So if damp-heat evils invade, it will combine with the vivodampness and consequently lead to imbalance of yin and yang and induce immunologicalresponse and result in immune imbalance and cytokine network disorders. It is these immune disorders that induce the imbalance between yin and yang and the lingering andrefractory pathological changes in GDS.